Thy-1 is the most abundant glycoprotein in rat neurons and appears during normal development at the time of neuronal differentiation and synaptogenesis. Homologous Thy-1 molecules exist in species from invertebrates to man. As previously shown by the principal investigator, antibodies against Thy-1 enhance the regeneration of neurites by rat retinal ganglion cells in culture (Leifer et al., Science 1984; 224:303-306). Additional knowledge about Thy-1 thus should contribute to a better understanding of congenital anomalies in which abnormal central nervous system morphogenesis is accompanied by mental retardation, intractable epilepsy, and motor system disorders. Moreover, further studies of the role of Thy-I in regeneration may make it possible to treat injuries to the brain, such as those induced by perinatal hypoxia and ischemia, which are also prominent causes of mental retardation, epilepsy, and motor disorders, especially spasticity and choreothetosis. Preliminary experiments by Drs. Lipton and Neve have tentativelv identified a Thy-1 receptor and human CDNA clones coding for it. Such a receptor would be, in some way, analogous to antibodies against Thy-1 since both bind to Thy-1, and is therefore likely to influence the growth of neuronal processes. We propose in this grant first to identify definitively and characterize a Thy-l receptor by using molecular biological techniques. Subsequent experiments will study its expression during development, examine its effects on neurons growing in culture, and look for homologous molecules in different species.